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1.
ACR Open Rheumatol ; 2022 Jun 27.
Article in English | MEDLINE | ID: covidwho-1905771

ABSTRACT

OBJECTIVE: Two cohort studies in patients with multisystem inflammatory syndrome in children (MIS-C) demonstrated contrasting results regarding the benefit of initial immunomodulatory treatment with intravenous immunoglobulin (IVIG) alone versus IVIG and glucocorticoids. We sought to determine whether application of different MIS-C definitions and differing disease severity between cohorts underlay discrepant results. METHODS: The Overcoming COVID-19 Public Health Surveillance Registry (OC-19) included patients meeting the US Centers for Disease Control and Prevention (CDC) MIS-C definition, whereas the Best Available Treatment Study (BATS) applied the World Health Organization (WHO) definition. We applied the WHO definition to the OC-19 cohort and the CDC definition to the BATS cohort and determined the proportion that did not meet the alternate definition. We compared illness severity indicators between cohorts. RESULTS: Of 349 OC-19 patients, 9.5% did not meet the WHO definition. Of 350 BATS patients, 10.3% did not meet the CDC definition. Most organ system involvement was similar between the cohorts, but more OC-19 patients had WHO-defined cardiac involvement (87.1% vs 79.4%, P = 0.008). OC-19 patients were more often admitted to intensive care (61.0% vs 44.8%, P < 0.001) and more often received vasopressors or inotropes (39.5% vs 22.9%, P < 0.001) before immunomodulatory treatment. CONCLUSION: Greater illness severity and cardiovascular involvement in the OC-19 cohort compared with the BATS cohort, and not use of different MIS-C case definitions, may have contributed to differing study conclusions about optimal initial treatment for MIS-C. Disease severity should be considered in future MIS-C study designs and treatment recommendations to identify patients who would benefit from aggressive immunomodulatory treatment.

2.
Lancet Child Adolesc Health ; 6(5): 281-282, 2022 05.
Article in English | MEDLINE | ID: covidwho-1698270
3.
Arthritis Rheumatol ; 74(4): e1-e20, 2022 04.
Article in English | MEDLINE | ID: covidwho-1669371

ABSTRACT

OBJECTIVE: To provide guidance on the management of Multisystem Inflammatory Syndrome in Children (MIS-C), a condition characterized by fever, inflammation, and multiorgan dysfunction that manifests late in the course of SARS-CoV-2 infection. Recommendations are also provided for children with hyperinflammation during COVID-19, the acute, infectious phase of SARS-CoV-2 infection. METHODS: The Task Force is composed of 9 pediatric rheumatologists and 2 adult rheumatologists, 2 pediatric cardiologists, 2 pediatric infectious disease specialists, and 1 pediatric critical care physician. Preliminary statements addressing clinical questions related to MIS-C and hyperinflammation in COVID-19 were developed based on evidence reports. Consensus was built through a modified Delphi process that involved anonymous voting and webinar discussion. A 9-point scale was used to determine the appropriateness of each statement (median scores of 1-3 for inappropriate, 4-6 for uncertain, and 7-9 for appropriate). Consensus was rated as low, moderate, or high based on dispersion of the votes. Approved guidance statements were those that were classified as appropriate with moderate or high levels of consensus, which were prespecified before voting. RESULTS: The guidance was approved in June 2020 and updated in November 2020 and October 2021, and consists of 41 final guidance statements accompanied by flow diagrams depicting the diagnostic pathway for MIS-C and recommendations for initial immunomodulatory treatment of MIS-C. CONCLUSION: Our understanding of SARS-CoV-2-related syndromes in the pediatric population continues to evolve. This guidance document reflects currently available evidence coupled with expert opinion, and will be revised as further evidence becomes available.


Subject(s)
COVID-19 , Rheumatology , Adult , COVID-19/complications , Child , Humans , SARS-CoV-2 , Systemic Inflammatory Response Syndrome/therapy , United States
4.
NPJ Digit Med ; 5(1): 9, 2022 Jan 20.
Article in English | MEDLINE | ID: covidwho-1635827

ABSTRACT

During the critical early stages of an emerging pandemic, limited availability of pathogen-specific testing can severely inhibit individualized risk screening and pandemic tracking. Standard clinical laboratory tests offer a widely available complementary data source for first-line risk screening and pandemic surveillance. Here, we propose an integrated framework for developing clinical-laboratory indicators for novel pandemics that combines population-level and individual-level analyses. We apply this framework to 7,520,834 clinical laboratory tests recorded over five years and find clinical-lab-test combinations that are strongly associated with SARS-CoV-2 PCR test results and Multisystem Inflammatory Syndrome in Children (MIS-C) diagnoses: Interleukin-related tests (e.g. IL4, IL10) were most strongly associated with SARS-CoV-2 infection and MIS-C, while other more widely available tests (ferritin, D-dimer, fibrinogen, alanine transaminase, and C-reactive protein) also had strong associations. When novel pandemics emerge, this framework can be used to identify specific combinations of clinical laboratory tests for public health tracking and first-line individualized risk screening.

6.
EClinicalMedicine ; 40: 101112, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1377702

ABSTRACT

BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) consensus criteria were designed for maximal sensitivity and therefore capture patients with acute COVID-19 pneumonia. METHODS: We performed unsupervised clustering on data from 1,526 patients (684 labeled MIS-C by clinicians) <21 years old hospitalized with COVID-19-related illness admitted between 15 March 2020 and 31 December 2020. We compared prevalence of assigned MIS-C labels and clinical features among clusters, followed by recursive feature elimination to identify characteristics of potentially misclassified MIS-C-labeled patients. FINDINGS: Of 94 clinical features tested, 46 were retained for clustering. Cluster 1 patients (N = 498; 92% labeled MIS-C) were mostly previously healthy (71%), with mean age 7·2 ± 0·4 years, predominant cardiovascular (77%) and/or mucocutaneous (82%) involvement, high inflammatory biomarkers, and mostly SARS-CoV-2 PCR negative (60%). Cluster 2 patients (N = 445; 27% labeled MIS-C) frequently had pre-existing conditions (79%, with 39% respiratory), were similarly 7·4 ± 2·1 years old, and commonly had chest radiograph infiltrates (79%) and positive PCR testing (90%). Cluster 3 patients (N = 583; 19% labeled MIS-C) were younger (2·8 ± 2·0 y), PCR positive (86%), with less inflammation. Radiographic findings of pulmonary infiltrates and positive SARS-CoV-2 PCR accurately distinguished cluster 2 MIS-C labeled patients from cluster 1 patients. INTERPRETATION: Using a data driven, unsupervised approach, we identified features that cluster patients into a group with high likelihood of having MIS-C. Other features identified a cluster of patients more likely to have acute severe COVID-19 pulmonary disease, and patients in this cluster labeled by clinicians as MIS-C may be misclassified. These data driven phenotypes may help refine the diagnosis of MIS-C.

8.
N Engl J Med ; 385(1): 23-34, 2021 07 01.
Article in English | MEDLINE | ID: covidwho-1270704

ABSTRACT

BACKGROUND: The assessment of real-world effectiveness of immunomodulatory medications for multisystem inflammatory syndrome in children (MIS-C) may guide therapy. METHODS: We analyzed surveillance data on inpatients younger than 21 years of age who had MIS-C and were admitted to 1 of 58 U.S. hospitals between March 15 and October 31, 2020. The effectiveness of initial immunomodulatory therapy (day 0, indicating the first day any such therapy for MIS-C was given) with intravenous immune globulin (IVIG) plus glucocorticoids, as compared with IVIG alone, was evaluated with propensity-score matching and inverse probability weighting, with adjustment for baseline MIS-C severity and demographic characteristics. The primary outcome was cardiovascular dysfunction (a composite of left ventricular dysfunction or shock resulting in the use of vasopressors) on or after day 2. Secondary outcomes included the components of the primary outcome, the receipt of adjunctive treatment (glucocorticoids in patients not already receiving glucocorticoids on day 0, a biologic, or a second dose of IVIG) on or after day 1, and persistent or recurrent fever on or after day 2. RESULTS: A total of 518 patients with MIS-C (median age, 8.7 years) received at least one immunomodulatory therapy; 75% had been previously healthy, and 9 died. In the propensity-score-matched analysis, initial treatment with IVIG plus glucocorticoids (103 patients) was associated with a lower risk of cardiovascular dysfunction on or after day 2 than IVIG alone (103 patients) (17% vs. 31%; risk ratio, 0.56; 95% confidence interval [CI], 0.34 to 0.94). The risks of the components of the composite outcome were also lower among those who received IVIG plus glucocorticoids: left ventricular dysfunction occurred in 8% and 17% of the patients, respectively (risk ratio, 0.46; 95% CI, 0.19 to 1.15), and shock resulting in vasopressor use in 13% and 24% (risk ratio, 0.54; 95% CI, 0.29 to 1.00). The use of adjunctive therapy was lower among patients who received IVIG plus glucocorticoids than among those who received IVIG alone (34% vs. 70%; risk ratio, 0.49; 95% CI, 0.36 to 0.65), but the risk of fever was unaffected (31% and 40%, respectively; risk ratio, 0.78; 95% CI, 0.53 to 1.13). The inverse-probability-weighted analysis confirmed the results of the propensity-score-matched analysis. CONCLUSIONS: Among children and adolescents with MIS-C, initial treatment with IVIG plus glucocorticoids was associated with a lower risk of new or persistent cardiovascular dysfunction than IVIG alone. (Funded by the Centers for Disease Control and Prevention.).


Subject(s)
COVID-19/drug therapy , Glucocorticoids/therapeutic use , Immunoglobulins, Intravenous/therapeutic use , Systemic Inflammatory Response Syndrome/drug therapy , Ventricular Dysfunction, Left/prevention & control , Adolescent , COVID-19/complications , COVID-19/immunology , COVID-19/mortality , Child , Child, Preschool , Cohort Studies , Combined Modality Therapy , Drug Therapy, Combination , Female , Hospitalization , Humans , Immunomodulation , Infant , Logistic Models , Male , Propensity Score , Public Health Surveillance , Shock/etiology , Shock/prevention & control , Systemic Inflammatory Response Syndrome/complications , Systemic Inflammatory Response Syndrome/immunology , Systemic Inflammatory Response Syndrome/mortality , Treatment Outcome , Ventricular Dysfunction, Left/etiology , Young Adult
10.
N Engl J Med ; 383(4): 334-346, 2020 07 23.
Article in English | MEDLINE | ID: covidwho-1254114

ABSTRACT

BACKGROUND: Understanding the epidemiology and clinical course of multisystem inflammatory syndrome in children (MIS-C) and its temporal association with coronavirus disease 2019 (Covid-19) is important, given the clinical and public health implications of the syndrome. METHODS: We conducted targeted surveillance for MIS-C from March 15 to May 20, 2020, in pediatric health centers across the United States. The case definition included six criteria: serious illness leading to hospitalization, an age of less than 21 years, fever that lasted for at least 24 hours, laboratory evidence of inflammation, multisystem organ involvement, and evidence of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) based on reverse-transcriptase polymerase chain reaction (RT-PCR), antibody testing, or exposure to persons with Covid-19 in the past month. Clinicians abstracted the data onto standardized forms. RESULTS: We report on 186 patients with MIS-C in 26 states. The median age was 8.3 years, 115 patients (62%) were male, 135 (73%) had previously been healthy, 131 (70%) were positive for SARS-CoV-2 by RT-PCR or antibody testing, and 164 (88%) were hospitalized after April 16, 2020. Organ-system involvement included the gastrointestinal system in 171 patients (92%), cardiovascular in 149 (80%), hematologic in 142 (76%), mucocutaneous in 137 (74%), and respiratory in 131 (70%). The median duration of hospitalization was 7 days (interquartile range, 4 to 10); 148 patients (80%) received intensive care, 37 (20%) received mechanical ventilation, 90 (48%) received vasoactive support, and 4 (2%) died. Coronary-artery aneurysms (z scores ≥2.5) were documented in 15 patients (8%), and Kawasaki's disease-like features were documented in 74 (40%). Most patients (171 [92%]) had elevations in at least four biomarkers indicating inflammation. The use of immunomodulating therapies was common: intravenous immune globulin was used in 144 (77%), glucocorticoids in 91 (49%), and interleukin-6 or 1RA inhibitors in 38 (20%). CONCLUSIONS: Multisystem inflammatory syndrome in children associated with SARS-CoV-2 led to serious and life-threatening illness in previously healthy children and adolescents. (Funded by the Centers for Disease Control and Prevention.).


Subject(s)
Coronavirus Infections/complications , Pneumonia, Viral/complications , Systemic Inflammatory Response Syndrome/epidemiology , Systemic Inflammatory Response Syndrome/virology , Adolescent , Betacoronavirus , COVID-19 , Centers for Disease Control and Prevention, U.S. , Child , Coronavirus Infections/epidemiology , Coronavirus Infections/therapy , Critical Care , Female , Glucocorticoids/therapeutic use , Humans , Immunoglobulins, Intravenous/therapeutic use , Immunomodulation , Inflammation , Length of Stay , Male , Mucocutaneous Lymph Node Syndrome/epidemiology , Mucocutaneous Lymph Node Syndrome/therapy , Mucocutaneous Lymph Node Syndrome/virology , Pandemics , Pneumonia, Viral/epidemiology , Pneumonia, Viral/therapy , Prospective Studies , Respiration, Artificial , Retrospective Studies , SARS-CoV-2 , Systemic Inflammatory Response Syndrome/therapy , United States
11.
JAMA ; 325(11): 1074-1087, 2021 03 16.
Article in English | MEDLINE | ID: covidwho-1168763

ABSTRACT

Importance: Refinement of criteria for multisystem inflammatory syndrome in children (MIS-C) may inform efforts to improve health outcomes. Objective: To compare clinical characteristics and outcomes of children and adolescents with MIS-C vs those with severe coronavirus disease 2019 (COVID-19). Setting, Design, and Participants: Case series of 1116 patients aged younger than 21 years hospitalized between March 15 and October 31, 2020, at 66 US hospitals in 31 states. Final date of follow-up was January 5, 2021. Patients with MIS-C had fever, inflammation, multisystem involvement, and positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reverse transcriptase-polymerase chain reaction (RT-PCR) or antibody test results or recent exposure with no alternate diagnosis. Patients with COVID-19 had positive RT-PCR test results and severe organ system involvement. Exposure: SARS-CoV-2. Main Outcomes and Measures: Presenting symptoms, organ system complications, laboratory biomarkers, interventions, and clinical outcomes. Multivariable regression was used to compute adjusted risk ratios (aRRs) of factors associated with MIS-C vs COVID-19. Results: Of 1116 patients (median age, 9.7 years; 45% female), 539 (48%) were diagnosed with MIS-C and 577 (52%) with COVID-19. Compared with patients with COVID-19, patients with MIS-C were more likely to be 6 to 12 years old (40.8% vs 19.4%; absolute risk difference [RD], 21.4% [95% CI, 16.1%-26.7%]; aRR, 1.51 [95% CI, 1.33-1.72] vs 0-5 years) and non-Hispanic Black (32.3% vs 21.5%; RD, 10.8% [95% CI, 5.6%-16.0%]; aRR, 1.43 [95% CI, 1.17-1.76] vs White). Compared with patients with COVID-19, patients with MIS-C were more likely to have cardiorespiratory involvement (56.0% vs 8.8%; RD, 47.2% [95% CI, 42.4%-52.0%]; aRR, 2.99 [95% CI, 2.55-3.50] vs respiratory involvement), cardiovascular without respiratory involvement (10.6% vs 2.9%; RD, 7.7% [95% CI, 4.7%-10.6%]; aRR, 2.49 [95% CI, 2.05-3.02] vs respiratory involvement), and mucocutaneous without cardiorespiratory involvement (7.1% vs 2.3%; RD, 4.8% [95% CI, 2.3%-7.3%]; aRR, 2.29 [95% CI, 1.84-2.85] vs respiratory involvement). Patients with MIS-C had higher neutrophil to lymphocyte ratio (median, 6.4 vs 2.7, P < .001), higher C-reactive protein level (median, 152 mg/L vs 33 mg/L; P < .001), and lower platelet count (<150 ×103 cells/µL [212/523 {41%} vs 84/486 {17%}, P < .001]). A total of 398 patients (73.8%) with MIS-C and 253 (43.8%) with COVID-19 were admitted to the intensive care unit, and 10 (1.9%) with MIS-C and 8 (1.4%) with COVID-19 died during hospitalization. Among patients with MIS-C with reduced left ventricular systolic function (172/503, 34.2%) and coronary artery aneurysm (57/424, 13.4%), an estimated 91.0% (95% CI, 86.0%-94.7%) and 79.1% (95% CI, 67.1%-89.1%), respectively, normalized within 30 days. Conclusions and Relevance: This case series of patients with MIS-C and with COVID-19 identified patterns of clinical presentation and organ system involvement. These patterns may help differentiate between MIS-C and COVID-19.


Subject(s)
COVID-19 , Systemic Inflammatory Response Syndrome , Adolescent , Age Factors , Biomarkers/analysis , COVID-19/complications , COVID-19/diagnosis , COVID-19/physiopathology , COVID-19/therapy , Child , Child, Preschool , Diagnosis, Differential , Female , Humans , Intensive Care Units, Pediatric , Male , Patient Acuity , Regression Analysis , Stroke Volume , Systemic Inflammatory Response Syndrome/complications , Systemic Inflammatory Response Syndrome/diagnosis , Systemic Inflammatory Response Syndrome/physiopathology , Systemic Inflammatory Response Syndrome/therapy , United States , Young Adult
12.
Pediatr Infect Dis J ; 40(4): e159-e161, 2021 04 01.
Article in English | MEDLINE | ID: covidwho-1132631

ABSTRACT

Multisystem inflammatory syndrome in children following severe acute respiratory syndrome coronavirus 2 infection is characterized by fever, elevated inflammatory markers, and multisystem organ involvement. Presentations are variable but often include gastrointestinal symptoms. We describe 5 children with fever and gastrointestinal symptoms initially concerning for multisystem inflammatory syndrome in children who were ultimately diagnosed with bacterial enteritis, highlighting the diagnostic challenges presented by the severe acute respiratory syndrome coronavirus 2 pandemic.


Subject(s)
Bacterial Infections/diagnosis , Enteritis/diagnosis , Systemic Inflammatory Response Syndrome/diagnosis , Bacterial Infections/microbiology , Biomarkers , Child , Child, Preschool , Diagnosis, Differential , Diagnostic Errors , Enteritis/microbiology , Female , Hospitalization , Humans , Male , Symptom Assessment
13.
JAMA Neurol ; 78(5): 536-547, 2021 05 01.
Article in English | MEDLINE | ID: covidwho-1118065

ABSTRACT

Importance: Coronavirus disease 2019 (COVID-19) affects the nervous system in adult patients. The spectrum of neurologic involvement in children and adolescents is unclear. Objective: To understand the range and severity of neurologic involvement among children and adolescents associated with COVID-19. Setting, Design, and Participants: Case series of patients (age <21 years) hospitalized between March 15, 2020, and December 15, 2020, with positive severe acute respiratory syndrome coronavirus 2 test result (reverse transcriptase-polymerase chain reaction and/or antibody) at 61 US hospitals in the Overcoming COVID-19 public health registry, including 616 (36%) meeting criteria for multisystem inflammatory syndrome in children. Patients with neurologic involvement had acute neurologic signs, symptoms, or diseases on presentation or during hospitalization. Life-threatening involvement was adjudicated by experts based on clinical and/or neuroradiologic features. Exposures: Severe acute respiratory syndrome coronavirus 2. Main Outcomes and Measures: Type and severity of neurologic involvement, laboratory and imaging data, and outcomes (death or survival with new neurologic deficits) at hospital discharge. Results: Of 1695 patients (909 [54%] male; median [interquartile range] age, 9.1 [2.4-15.3] years), 365 (22%) from 52 sites had documented neurologic involvement. Patients with neurologic involvement were more likely to have underlying neurologic disorders (81 of 365 [22%]) compared with those without (113 of 1330 [8%]), but a similar number were previously healthy (195 [53%] vs 723 [54%]) and met criteria for multisystem inflammatory syndrome in children (126 [35%] vs 490 [37%]). Among those with neurologic involvement, 322 (88%) had transient symptoms and survived, and 43 (12%) developed life-threatening conditions clinically adjudicated to be associated with COVID-19, including severe encephalopathy (n = 15; 5 with splenial lesions), stroke (n = 12), central nervous system infection/demyelination (n = 8), Guillain-Barré syndrome/variants (n = 4), and acute fulminant cerebral edema (n = 4). Compared with those without life-threatening conditions (n = 322), those with life-threatening neurologic conditions had higher neutrophil-to-lymphocyte ratios (median, 12.2 vs 4.4) and higher reported frequency of D-dimer greater than 3 µg/mL fibrinogen equivalent units (21 [49%] vs 72 [22%]). Of 43 patients who developed COVID-19-related life-threatening neurologic involvement, 17 survivors (40%) had new neurologic deficits at hospital discharge, and 11 patients (26%) died. Conclusions and Relevance: In this study, many children and adolescents hospitalized for COVID-19 or multisystem inflammatory syndrome in children had neurologic involvement, mostly transient symptoms. A range of life-threatening and fatal neurologic conditions associated with COVID-19 infrequently occurred. Effects on long-term neurodevelopmental outcomes are unknown.


Subject(s)
COVID-19/complications , Nervous System Diseases/etiology , Systemic Inflammatory Response Syndrome/etiology , Adolescent , COVID-19/etiology , COVID-19/mortality , Child , Child, Preschool , Critical Care , Female , Hospitalization , Humans , Male , Nervous System Diseases/mortality , Patient Discharge/statistics & numerical data , Respiratory Distress Syndrome/etiology , Respiratory Distress Syndrome/therapy , Systemic Inflammatory Response Syndrome/complications , Treatment Outcome , United States/epidemiology
14.
Arthritis Rheumatol ; 73(4): e13-e29, 2021 Apr.
Article in English | MEDLINE | ID: covidwho-1086276

ABSTRACT

OBJECTIVE: To provide guidance on the management of Multisystem Inflammatory Syndrome in Children (MIS-C), a condition characterized by fever, inflammation, and multiorgan dysfunction that manifests late in the course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Recommendations are also provided for children with hyperinflammation during coronavirus disease 2019 (COVID-19), the acute, infectious phase of SARS-CoV-2 infection. METHODS: The Task Force was composed of 9 pediatric rheumatologists and 2 adult rheumatologists, 2 pediatric cardiologists, 2 pediatric infectious disease specialists, and 1 pediatric critical care physician. Preliminary statements addressing clinical questions related to MIS-C and hyperinflammation in COVID-19 were developed based on evidence reports. Consensus was built through a modified Delphi process that involved anonymous voting and webinar discussion. A 9-point scale was used to determine the appropriateness of each statement (median scores of 1-3 for inappropriate, 4-6 for uncertain, and 7-9 for appropriate). Consensus was rated as low, moderate, or high based on dispersion of the votes. Approved guidance statements were those that were classified as appropriate with moderate or high levels of consensus, which were prespecified before voting. RESULTS: The first version of the guidance was approved in June 2020, and consisted of 40 final guidance statements accompanied by a flow diagram depicting the diagnostic pathway for MIS-C. The document was revised in November 2020, and a new flow diagram with recommendations for initial immunomodulatory treatment of MIS-C was added. CONCLUSION: Our understanding of SARS-CoV-2-related syndromes in the pediatric population continues to evolve. This guidance document reflects currently available evidence coupled with expert opinion, and will be revised as further evidence becomes available.


Subject(s)
COVID-19/diagnosis , COVID-19/therapy , Systemic Inflammatory Response Syndrome/diagnosis , Systemic Inflammatory Response Syndrome/therapy , Adolescent , Advisory Committees , Anticoagulants/therapeutic use , Antirheumatic Agents/therapeutic use , Child , Child, Preschool , Delphi Technique , Diagnosis, Differential , Glucocorticoids/therapeutic use , Humans , Immunoglobulins, Intravenous/therapeutic use , Immunologic Factors/therapeutic use , Infant , Infant, Newborn , Inflammation , Interleukin 1 Receptor Antagonist Protein/therapeutic use , Mucocutaneous Lymph Node Syndrome/diagnosis , Platelet Aggregation Inhibitors/therapeutic use , Rheumatology , SARS-CoV-2 , Young Adult
15.
Eur J Pediatr ; 180(2): 307-322, 2021 Feb.
Article in English | MEDLINE | ID: covidwho-1064496

ABSTRACT

Initial reports on COVID-19 described children as largely spared from severe manifestations, with only 2-6% of children requiring intensive care treatment. However, since mid-April 2020, clusters of pediatric cases of severe systemic hyperinflammation and shock epidemiologically linked with COVID-19 have been reported. This condition was named as SARS-Cov-2-associated multisystem inflammatory syndrome in children and showed similarities to Kawasaki disease. Here, we present a narrative review of cases reported in literature and we discuss the clinical acute and follow-up management of these patients. Patients with SARS-Cov-2-associated multisystem inflammatory syndrome frequently presented with persistent fever, gastrointestinal symptoms, polymorphic rash, conjunctivitis, and mucosal changes. Elevated inflammatory markers and evidence of cytokine storm were frequently observed. A subset of these patients also presented with hypotension and shock (20-100%) from either acute myocardial dysfunction or systemic hyperinflammation/vasodilation. Coronary artery dilation or aneurysms have been described in 6-24%, and arrhythmias in 7-60%. Cardiac support, immunomodulation, and anticoagulation are the key aspects for the management of the acute phase. Long-term structured follow-up of these patients is required due to the unclear prognosis and risk of progression of cardiac manifestations.Conclusion: Multisystem inflammatory syndrome is a novel syndrome related to SARS-CoV-2 infection. Evidence is still scarce but rapidly emerging in the literature. Cardiac manifestations are frequent, including myocardial and coronary involvement, and need to be carefully identified and monitored over time. What is Known: • Multisystem inflammatory syndrome in children (MIS-C) has been described associated with SARS-CoV-2. What is New: • Patients with MIS-C often present with fever, gastrointestinal symptoms, and shock. • Cardiac involvement is found in a high proportion of these patients, including ventricular dysfunction, coronary artery dilation or aneurysm, and arrhythmias. • Management is based on expert consensus and includes cardiac support, immunomodulatory agents, and anticoagulation. • Long-term follow-up is required due to the unclear prognosis and risk of progression of cardiac manifestation.


Subject(s)
COVID-19/complications , Heart Diseases/etiology , SARS-CoV-2 , Systemic Inflammatory Response Syndrome/complications , Child , Critical Care/statistics & numerical data , Humans
16.
Pediatrics ; 146(5)2020 11.
Article in English | MEDLINE | ID: covidwho-902104

ABSTRACT

BACKGROUND: Children are at risk for multisystem inflammatory syndrome in children (MIS-C) after infection with severe acute respiratory syndrome coronavirus 2. Cardiovascular complications, including ventricular dysfunction and coronary dilation, are frequent, but there are limited data on arrhythmic complications. METHODS: Retrospective cohort study of children and young adults aged ≤21 years admitted with MIS-C. Demographic characteristics, electrocardiogram (ECG) and echocardiogram findings, and hospital course were described. RESULTS: Among 25 patients admitted with MIS-C (60% male; median age 9.7 [interquartile range 2.7-15.0] years), ECG anomalies were found in 14 (56%). First-degree atrioventricular block (AVB) was seen in 5 (20%) patients a median of 6 (interquartile range 5-8) days after onset of fever and progressed to second- or third-degree AVB in 4 patients. No patient required intervention for AVB. All patients with AVB were admitted to the ICU (before onset of AVB) and had ventricular dysfunction on echocardiograms. All patients with second- or third-degree AVB had elevated brain natriuretic peptide levels, whereas the patient with first-degree AVB had a normal brain natriuretic peptide level. No patient with AVB had an elevated troponin level. QTc prolongation was seen in 7 patients (28%), and nonspecific ST segment changes were seen in 14 patients (56%). Ectopic atrial tachycardia was observed in 1 patient, and none developed ventricular arrhythmias. CONCLUSIONS: Children with MIS-C are at risk for atrioventricular conduction disease, especially those who require ICU admission and have ventricular dysfunction. ECGs should be monitored for evidence of PR prolongation. Continuous telemetry may be required in patients with evidence of first-degree AVB because of risk of progression to high-grade AVB.


Subject(s)
Atrioventricular Block/etiology , Betacoronavirus , Coronavirus Infections/complications , Pneumonia, Viral/complications , Systemic Inflammatory Response Syndrome/complications , Adolescent , Atrioventricular Block/diagnosis , Atrioventricular Block/epidemiology , COVID-19 , Child , Child, Preschool , Female , Follow-Up Studies , Humans , Infant , Infant, Newborn , Male , Pandemics , Retrospective Studies , Risk Factors , SARS-CoV-2 , Young Adult
17.
J Clin Invest ; 130(11): 5942-5950, 2020 11 02.
Article in English | MEDLINE | ID: covidwho-670865

ABSTRACT

BACKGROUNDPediatric SARS-CoV-2 infection can be complicated by a dangerous hyperinflammatory condition termed multisystem inflammatory syndrome in children (MIS-C). The clinical and immunologic spectrum of MIS-C and its relationship to other inflammatory conditions of childhood have not been studied in detail.METHODSWe retrospectively studied confirmed cases of MIS-C at our institution from March to June 2020. The clinical characteristics, laboratory studies, and treatment response were collected. Data were compared with historic cohorts of Kawasaki disease (KD) and macrophage activation syndrome (MAS).RESULTSTwenty-eight patients fulfilled the case definition of MIS-C. Median age at presentation was 9 years (range: 1 month to 17 years); 50% of patients had preexisting conditions. All patients had laboratory confirmation of SARS-CoV-2 infection. Seventeen patients (61%) required intensive care, including 7 patients (25%) who required inotrope support. Seven patients (25%) met criteria for complete or incomplete KD, and coronary abnormalities were found in 6 cases. Lymphopenia, thrombocytopenia, and elevation in inflammatory markers, D-dimer, B-type natriuretic peptide, IL-6, and IL-10 levels were common but not ubiquitous. Cytopenias distinguished MIS-C from KD and the degree of hyperferritinemia and pattern of cytokine production differed between MIS-C and MAS. Immunomodulatory therapy given to patients with MIS-C included intravenous immune globulin (IVIG) (71%), corticosteroids (61%), and anakinra (18%). Clinical and laboratory improvement were observed in all cases, including 6 cases that did not require immunomodulatory therapy. No mortality was recorded in this cohort.CONCLUSIONMIS-C encompasses a broad phenotypic spectrum with clinical and laboratory features distinct from KD and MAS.FUNDINGThis work was supported by the National Institutes of Health, National Institute of Arthritis and Musculoskeletal and Skin Diseases; the National Institute of Allergy and Infectious Diseases; Rheumatology Research Foundation Investigator Awards and Medical Education Award; Boston Children's Hospital Faculty Career Development Awards; the McCance Family Foundation; and the Samara Jan Turkel Center.


Subject(s)
Adrenal Cortex Hormones/administration & dosage , Betacoronavirus/metabolism , Immunoglobulins, Intravenous/administration & dosage , Immunomodulation , Interleukin 1 Receptor Antagonist Protein/administration & dosage , Systemic Inflammatory Response Syndrome , Adolescent , Biomarkers/blood , COVID-19 , Child , Child, Preschool , Female , Fibrin Fibrinogen Degradation Products/metabolism , Humans , Infant , Interleukin-10/blood , Interleukin-6/blood , Macrophage Activation Syndrome/blood , Macrophage Activation Syndrome/diagnosis , Macrophage Activation Syndrome/drug therapy , Macrophage Activation Syndrome/immunology , Male , Mucocutaneous Lymph Node Syndrome/blood , Mucocutaneous Lymph Node Syndrome/diagnosis , Mucocutaneous Lymph Node Syndrome/drug therapy , Mucocutaneous Lymph Node Syndrome/immunology , Natriuretic Peptide, Brain/blood , Retrospective Studies , SARS-CoV-2 , Systemic Inflammatory Response Syndrome/blood , Systemic Inflammatory Response Syndrome/diagnosis , Systemic Inflammatory Response Syndrome/drug therapy , Systemic Inflammatory Response Syndrome/immunology
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